Aging exacerbates damage and delays repair of alveolar epithelia following influenza viral pneumonia

Background

Influenza virus infection causes significantly higher levels of morbidity and mortality in the elderly. Studies have shown that impaired immunity in the elderly contributes to the increased susceptibility to influenza virus infection, however, how aging affects the lung tissue damage and repair has not been completely elucidated.

Methods

Aged (16–18 months old) and young (2–3 months old) mice were infected with influenza virus intratracheally. Body weight and mortality were monitored. Different days after infection, lung sections were stained to estimate the overall lung tissue damage and for club cells, pro-SPC⁺ bronchiolar epithelial cells, alveolar type I and II cells to quantify their frequencies using automated image analysis algorithms.

Results

Following influenza infection, aged mice lose more weight and die from otherwise sub-lethal influenza infection in young mice. Although there is no difference in damage and regeneration of club cells between the young and the aged mice, damage to alveolar type I and II cells (AT1s and AT2s) is exacerbated, and regeneration of AT2s and their precursors (pro-SPC-positive bronchiolar epithelial cells) is significantly delayed in the aged mice. We further show that oseltamivir treatment reduces virus load and lung damage, and promotes pulmonary recovery from infection in the aged mice.

Conclusions

These findings show that aging increases susceptibility of the distal lung epithelium to influenza infection and delays the emergence of pro-SPC positive progenitor cells during the repair process. Our findings also shed light on possible approaches to enhance the clinical management of severe influenza pneumonia in the elderly.

Electronic supplementary material

The online version of this article (doi:10.1186/s12931-014-0116-z) contains supplementary material, which is available to authorized users.     

The effect of modification of tRNA nucleotide-37 on the tRNA interaction with the P- and A-site of the 70S ribosome Escherichia coli

A modified nucleotide on the 3'-side of the anticodon loop of tRNA is one of the most important structure element regulating codon-anticodone interaction on the ribosome owing to the stacking interaction with the stack of codon-anticodon bases. The presence and identity (pyrimidine, purine or modified purine) of this nucleotide has an essential influence on the energy of the stacking interaction on A- and P-sites of the ribosome. There is a significant influence of the 37-modification by itself on the P-site, whereas there is no such one on the A-site of the ribosome. Comparison of binding enthalpies of tRNA interactions on the P- or A-site of the ribosome with the binding enthalpies of the complex of two tRNAs with the complementary anticodones suggests that the ribosome by itself significantly endows in the thermodynamics of codon-anticodon complex formation. It happens by additional ribosomal interactions with the molecule of tRNA or indirectly by the stabilization of codon-anticodon conformation. In addition to the stacking, tRNA binding in the A and P sites is futher stabilized by the interactions involving some magnesium ions. The number of them involved in those interactions strongly depends on the nucleotide identity in the 37-position of tRNA anticodon loop.     

Effect of Rhizobium leguminosarum 252 agglutinins on the activity of some plant cell enzymes]

The incubation of pea seedling roots with the surface agglutinins R1 and R2 of Rhizobium leguminosarum 252 brought about an increase in the activity of proteases, beta-glucosidase, and, especially, succinate dehydrogenase in the roots. The data presented show that rhizobial agglutinins play an important part in the formation and functioning of legume-rhizobial associations.     

Multilevel regulation of steroid synthesis and metabolism in the bovine placenta

Steroid hormones play critical roles in almost all physiological processes in male and female reproduction. In a normal pregnancy, the concentrations of steroid hormones in maternal and foetal blood vary with gestation in response to changing needs. The placenta plays a central role in producing the appropriate steroids to support the pregnancy by coordinating its own steroidogenic activity with that of the corpus luteum and responding to foetal signals. Although much is known about the steroidogenic potential of the bovine placenta, far less is known about how the placenta integrates the synthesis of steroids with their subsequent metabolism and clearance to achieve appropriate local and peripheral concentrations of steroids in maternal and foetal blood at each stage of gestation. This review focuses on the current knowledge of the temporal and spatial regulation and compartmentalization of the biochemical pathways by which potent steroid hormones are synthesized and metabolized in the bovine placenta. The aim is to increase our understanding of how the balance of synthesis and metabolism determines placental steroid output as it changes with development and differentiation, and how this is regulated in response to the variations in the foetal signals and luteal secretory activity. The review highlights knowledge gaps and suggests that mathematical modelling can help understand the effect of different levels of regulation on the steroidogenic output of an organ, such as the bovine placenta.     

Development of a 3D finite element model of lens microcirculation

Background

It has been proposed that in the absence of a blood supply, the ocular lens operates an internal microcirculation system. This system delivers nutrients, removes waste products and maintains ionic homeostasis in the lens. The microcirculation is generated by spatial differences in membrane transport properties; and previously has been modelled by an equivalent electrical circuit and solved analytically. While effective, this approach did not fully account for all the anatomical and functional complexities of the lens. To encapsulate these complexities we have created a 3D finite element computer model of the lens.

Methods

Initially, we created an anatomically-correct representative mesh of the lens. We then implemented the Stokes and advective Nernst-Plank equations, in order to model the water and ion fluxes respectively. Next we complemented the model with experimentally-measured surface ionic concentrations as boundary conditions and solved it.

Results

Our model calculated the standing ionic concentrations and electrical potential gradients in the lens. Furthermore, it generated vector maps of intra- and extracellular space ion and water fluxes that are proposed to circulate throughout the lens. These fields have only been measured on the surface of the lens and our calculations are the first 3D representation of their direction and magnitude in the lens.

Conclusion

Values for steady state standing fields for concentration and electrical potential plus ionic and fluid fluxes calculated by our model exhibited broad agreement with observed experimental values. Our model of lens function represents a platform to integrate new experimental data as they emerge and assist us to understand how the integrated structure and function of the lens contributes to the maintenance of its transparency.     

Sustained release of the antitumor drug paclitaxel from poly(3-hydroxybutyrate)-based microspheres

The development of sustained release formulations based on biodegradable polymers is a promising trend in modern pharmacology. Polyhydroxyalkanoates (PHA) attract increasing attention due to their biodegradability and high biocompatibility, which make them suitable for the development of novel drug dosage forms. We have produced poly(3-hydroxybutyrate) (PHB)-based microspheres loaded with the antitumor drug paclitaxel and investigated morphology, drug release kinetics and the effect of these microspheres on tumor cells in vitro. The data on the kinetics of drug release, biocompatibility and biological activity of the biopolymer microspheres in vitro have demonstrated that the studied system of prolonged drug release had lower toxicity and higher efficiency compared to the traditional dosage forms of paclitaxel.